JS1.4 Neurological follow-up of neurotoxicity after CAR T cell therapy in lymphoma patients: A French neurological multi-center survey

Abstract

Abstract BACKGROUND Chimeric antigen receptor-modified T (CAR T) cell therapy is a highly promising treatment for haematological malignancies but is frequently associated with cytokine-release syndrome (CRS) and neurotoxicity. The physiopathological mechanisms of neurological complications and their links with CRS remain largely unknown. The aims of this study are: a) to follow-up longitudinally patients treated with CAR-T cell therapy; b) to exhaustively identify neurological signs and symptoms and; c) to describe their occurrence over time. MATERIAL AND METHODS Since September 2018, all patients treated with CD19-targeted CAR T cell therapy for relapsing lymphoma were systematically followed-up and monitored for signs of neurotoxicity by a neurologist. Five different centres (Paris-Saint-Louis, Nantes, Lyon, Montpellier, and Rennes) participated in this study. RESULTS As of April 1st 2019, 57 patients, mean age 49 years (range from 22 to 72 years, median age 50 years), 22 females / 35 males, all treated for lymphoma, were included in this study Neurotoxicity, defined as the presence of at least one neurological sign or symptoms appearing after treatment infusion, was present in 33 % of patients. The median time to onset was 7.5 days after infusion with a median duration of symptoms of 5 days. Neurological symptoms were: Encephalopathy (52%), cerebellar syndrome (26%), aphasia (15%), agraphia (15%), executive syndrome (10%), myoclonus (10%), dysarthria (10%), meningismus (5%), transverse myelitis (5%), seizure (5%), neuralgia (5%), and dysesthesia (5%). The severity grade of neurotoxicity was grade 4: 2 patients, Grade 3: 7 patients, grade 2: 5 patients and grade 1: 5 patients (CTCAE grading). CRS was observed in 75% of patients. All patients who developed neurological disorders also had CRS (grade 1: 68%, grade 2: 10%, grade 3: 15%, grade 4: 5%) that preceded neurotoxicity. As the study is still ongoing, updated results will be presented at the EANO meeting. CONCLUSION Neurotoxicity associated with CAR-T therapies occurs in one third of patients. This high frequency underlines the need: 1 - to neurologically assess all patients before and repeatedly after therapy infusions; 2 - to provide guidelines for neurological assessment and relevant investigations to improve early recognition of neurotoxicity and its management